Seizure outcomes after thalamic deep brain stimulation in drug-resistant epilepsy: How electrode location, device platform, and epilepsy subtype drive response—A systematic review with pooled analysis

Deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT), centromedian nucleus (CM), and medial pulvinar nucleus (PuM) has emerged as a neuromodulatory intervention for adults with drug-resistant epilepsy (DRE). Despite growing clinical experience, no pooled analysis has integrated outcomes across all three thalamic targets. A PRISMA-compliant systematic search was conducted across PubMed, EMBASE, and Cochrane databases (January 2000–December 2025). Studies reporting seizure frequency reduction following thalamic DBS in ≥4 adults with DRE and ≥6 months of follow-up were included. Pooled descriptive statistics and weighted mean analyses were calculated within each target separately; subgroup comparisons by seizure onset zone and epilepsy classification were performed within each nucleus. Nineteen studies (651 patients) met inclusion criteria: ten ANT (n = 551), seven CM (n = 89), and two PuM (n = 11). Weighted mean seizure frequency reductions were 48.7% (ANT), 71.4% (CM), and 62.0% (PuM). Responder rates (≥50% reduction) were 48.7% (ANT), 76.2% (CM), and 60.0% (PuM). ANT DBS showed progressive improvement from year one (33%–41% reduction) through year five (56%–69% reduction). Temporal lobe origin predicted superior ANT outcomes. CM DBS was most effective for generalized epilepsy syndromes, including Lennox–Gastaut syndrome. PuM DBS yielded promising results for posterior quadrant and temporal-plus epilepsy. Adverse events were target-specific, including depression and memory impairment (ANT), postoperative drowsiness (CM), and hemorrhagic complications (PuM). No stimulation-related mortality occurred. Thalamic DBS provides durable seizure reduction across three nuclear targets, with efficacy varying by epilepsy classification and seizure onset zone. ANT DBS has Class I evidence supporting its use in focal epilepsies, particularly temporal lobe origin. CM DBS shows strong preliminary efficacy for generalized epilepsies, warranting larger randomized trials. PuM DBS requires prospective validation. Head-to-head comparative trials are needed before individualized target selection recommendations can be made.